دورية أكاديمية
Does the early aldosterone-induced SGK1 play a role in early Kaliuresis?
| العنوان: | Does the early aldosterone-induced SGK1 play a role in early Kaliuresis? |
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| المؤلفون: | Al-Qusairi, L., Basquin, D., Stifanelli, M., Welling, P.A., Staub, O. |
| المصدر: | Physiological reports, vol. 10, no. 4, pp. e15188 |
| سنة النشر: | 2022 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Aldosterone, Animals, Epithelial Sodium Channels/genetics, Mice, Nedd4 Ubiquitin Protein Ligases/genetics, Potassium/metabolism, Sodium/metabolism, Sodium Chloride, Dietary/metabolism, Solute Carrier Family 12, Member 3/genetics |
| الوصف: | Urinary K + potassium excretion rapidly increases after a potassium-rich meal. The early aldosterone-induced sgk1 gene (encoding serum and glucocorticoid-induced kinase 1), activates potassium clearance, but the role of this kinase in the early activation of K + secretion has not been clearly defined. Here, we challenged inducible renal-tubule-specific Sgk1 Pax8 / LC1 knockout mice with an acute high-potassium load (HK:5%K + ) and compared the physiological and molecular responses to control mice. We observe that urinary excretion after a K + load over the first 3 h is not dependent on SGK1 but is coincident with the rapid dephosphorylation of the Na + ,Cl - -cotransporter (NCC) to increase distal salt delivery. Molecular analyses indicate that whereas SGK1-mediated phosphorylation of the ubiquitin-protein ligase NEDD4-2 begins to increase by 3h, SGK1-dependent proteolytic activation of ENaC only becomes detectable after 6 h of HK intake. Consistent with SGK1-dependent ENaC activation via inhibition of NEDD4-2-mediated ubiquitylation, Sgk1 Pax8 / LC1 mice are unable to efficiently inhibit NEDD4-2 or increase ENaC cleavage after 6 h of HK. Nevertheless, no defect in acute K + balance was detected in the mutant mice after 6 h of HK. Moreover, we found that Sgk1 Pax8 / LC1 mice reduce NCC phosphorylation and NCC-mediated salt absorption to a greater extent than control mice after a K + load, promoting increased amiloride-sensitive Na + -reabsorption via ENaC to maintain adequate kaliuresis. Together, these data indicate that: (a) during the early 3 h of HK intake, K + excretion is SGK1-independent even under an extreme K + challenge, (b) shortly after, SGK1 inhibits NEDD4-2 and activates ENaC to stimulate K + -secretion, (c) SGK1-dependent phosphorylation of NCC occurs, acting more likely as a brake pedal to prevent excessive K + loss. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2051-817X |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35224872; info:eu-repo/semantics/altIdentifier/eissn/2051-817X; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_90DE4FDA5B157; https://serval.unil.ch/notice/serval:BIB_90DE4FDA5B15Test; urn:issn:2051-817X; https://serval.unil.ch/resource/serval:BIB_90DE4FDA5B15.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_90DE4FDA5B157Test |
| DOI: | 10.14814/phy2.15188 |
| الإتاحة: | https://doi.org/10.14814/phy2.15188Test https://serval.unil.ch/notice/serval:BIB_90DE4FDA5B15Test https://serval.unil.ch/resource/serval:BIB_90DE4FDA5B15.P001/REF.pdfTest http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_90DE4FDA5B157Test |
| حقوق: | info:eu-repo/semantics/openAccess ; CC BY 4.0 ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.D03CC0C2 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2051817X |
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| DOI: | 10.14814/phy2.15188 |